Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

Abstract

Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio.

Update on management of paediatric dyslipidaemia

“…Proprotein convertase subtilisin/kexin type 9 mAbs PCSK9 mAb decrease LDL-C level by inhibiting the PCSK9 mediated LDLR degradation by binding to circulating PCSK9. LDL-C reduction by 60-70% has been reported when using alone or in combination with statin [46][47][48][49][50][51][52][53][54][55][56]. Reduction in lipoprotein (a) (Lp (a)) by 18-36% and triglycerides by 12-31% has been noted as an additional beneficial effect [50,[57][58][59][60].…”

Novel therapeutic targets and agents for pediatric dyslipidemia

“…They reduce LDL-C by 60–70% when used alone or in combination therapy with statins. 45 – 55 They also reduce levels of lipoprotein(a) (Lp(a)] by 18–36% and TG by 12–31%. 52 , 56 – 59 Meta-analysis of data from subjects treated with PCSK9 mAb has shown reduced all-cause mortality, cardiovascular mortality, and myocardial infarction.…”

Correlations of PCSK9 and LDLR Gene Polymorphisms and Serum PCSK9 Levels With Atherosclerosis and Lipid Metabolism in Patients on Maintenance Hemodialysis

“…Proprotein convertase subtilisin/kexin type 9 (PCSK9) refers to a serine protease–modulating lipid metabolism associated with inflammation in acute coronary syndrome 7 . Discovered in 2003, PCSK9 subsequently emerges as an innovative target for low‐density lipoprotein cholesterol (LDL‐C)‐lowering treatment 8 . PCSK9 performs a crucial role in myocardial infarction 9 and in the regulation of lipid metabolism 10 .…”

“…7 Discovered in 2003, PCSK9 subsequently emerges as an innovative target for low-density lipoprotein cholesterol (LDL-C)lowering treatment. 8 PCSK9 performs a crucial role in myocardial infarction 9 and in the regulation of lipid metabolism. 10 PCSK9 is involved in vascular inflammation in atherosclerosis, and it is expressed by various cell types that are involved in atherosclerosis and is detected inside human atherosclerotic plaques.…”